BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To evaluate the reliability of a region-locked 3D-printed template combined with a bi-directional matching scheme in assistance of screw placement for thoracolumbar fractures.Methods:From January 2019 to March 2023, 52 patients with thoracolumbar fracture were treated at Department of Orthopedics, The People's Hospital of Liyang. They were 29 males and 23 females, with an age of (58.2±13.3) years. They were divided into a template group and a free-hand group according to the different screw placements. In the template group of 25 cases, a region-locked 3D-printed template combined with a bi-directional matching scheme was used to assist the pedicle positioning; in the free-hand group of 27 cases, the free hand screw placement was assisted only by image data and C-arm fluoroscopy. The operation time, intraoperative fluoroscopy frequency, intraoperative blood loss, complications, and placement accuracy were compared between the 2 groups. Visual analogue scale (VAS), Oswestry disability index (ODI), and anterior height ratio of the injured vertebra were compared between preoperation, 1 week postoperation, and the final follow-up, as well as between the 2 groups.Results:There were no statistically significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (11.2±4.2) months. The differences were not statistically significant between the 2 groups in intraoperative blood loss, rate of complications, VAS or ODI at preoperation, 1 week postoperation, or the final follow-up, or in anterior height ratio of the injured vertebra ( P>0.05). In the template group, the operation time [(80.1±18.5) min] was significantly longer than that in the free-hand group [(69.4±16.6) min], the intraoperative fluoroscopy frequency [2 (2, 3) times] significantly lower than that in the free-hand group [3 (3, 4) times], and the placement accuracy [98.4% (127/129)] significantly higher than that in the free-hand group [91.8% (112/122)] (all P<0.05). All patients showed significant improvements in VAS, ODI and anterior height ratio of the injured vertebra at postoperative 1 week compared with the preoperative values, and the improvements at the last follow-up were significantly larger than those at postoperative 1 week ( P<0.05). No injury to the spinal cord, nerve root or blood vessel was observed postoperatively. Conclusions:In the treatment of thoracolumbar fractures, the screw placement assisted by a region-locked 3D-printed template combined with a bi-directional matching scheme is better than free-hand screw placement in terms of improved accuracy and reduced fluoroscopy, but the former incurs longer operative exposure than the latter. There is no significant difference between the 2 methods of screw placement in clinical efficacy.

OBJECTIVE To explore the expression changes of TLR4/MyD88/NF-κB signaling pathways in olfactory disorders.METHODS There were 40 healthy BALB/c mice who were divided into an observation group and a control group,with 20 mice in each group.Detection of Toll-like receptors(TLR4),myeloid differentiation primary response gene 88(MyD88)and nuclear factor kappa B(NF-κB)in mice using quantitative reverse transcription PCR level;Detection of TLR4,MyD88 and NF-κB by Western blot(WB)test protein content;Immunohistochemical detection of the expression of mouse olfactory marker protein(OMP).RESULTS There was no significant difference in foraging time between the two groups of mice before modeling(P>0.05),after modeling,the foraging time of the observation group mice was significantly longer than that of the control group(P<0.05);The relative mRNA expression level of TLR4,MyD88 and NF-κB in the nasal epithelium of mice in the observation group was significantly higher than that of the control group(P<0.05);The protein expression of TLR4,MyD88 and NF-κB in the nasal epithelium of mice in the observation group was significantly higher than that of the control group(P<0.05);The level of OMP protein in the nasal epithelium of the observation group was significantly lower than that of the control group(P<0.05).CONCLUSION Expression reinforcement of TLR4/MyD88/NF-κB signaling pathway in a mouse model of olfactory dysfunction.

[Objective] To determine the feasibility of preparing plasminogen (Pg) with Fraction Ⅲ precipitation (hereinafter referred to as FⅢ-P) from low-temperature ethanol process by full chromatography (hereinafter referred to as FⅢ-P process). [Methods] The FⅢ-P was diluted with dissolution buffer at different dilution times and stirring time. The potency and antigen concentration of Pg in dissolution sample were detected and the dissolution and clarification conditions were determined. Pre-treatment of loading sample and pre-experiment of affinity chromatography were carried out on the FⅢ-P dissolution sample to judge whether the loading sample had an impact on the chromatography by observing the performance of the affinity chromatography column and to evaluate whether the affinity chromatography could achieve the purpose of purifying Pg by detecting the plasma protein antigen concentration and Pg potency of the samples in the process. Two batches of FⅢ-P process were studied step by step, and the specific activity, steps and total recovery, and the output of Pg per ton of plasma were calculated. The feasibility of preparing Pg by FⅢ-P process was evaluated by comparing with the data of full chromatography process using plasma as raw material (hereinafter referred to as plasma process). [Results] The FⅢ-P was dissolved with 10 times of dissolution buffer, stirred for 1 hour, centrifuged at room temperature of 10 000×g for 15 minutes. The supernatant was first filtered with a screen, then clarified with an 8/0.8 μm filter, and finally filtered with a 0.45/0.2 μm filter and loaded. Pre-test showed that from clarification and filtration to Pg affinity chromatography, the step recovery of activity and antigen was 39.51% and 108.64%, respectively, the antigen concentration of Pg increased by 31.16 times and the activity increased by 11.39 times after affinity chromatography, which reaching the effect of affinity chromatography purification of Pg. The results of 2 batches of step-by-step scale-up FⅢ-P process showed that the total recoveries of antigen and activity from plasma to SP chromatography of FⅢ-P process were (45.76±1.10)% and (24.15±0.59)%, respectively, which had a total loss of about 1/3 of antigen and about 2/3 of activity compared to the plasma process. The Pg specific activity of SP chromatography eluent was (4.68±0.25) U/mg, which was about half of that of plasma process, but meeted the internal standard of > 4 U/mg. The output of Pg antigen per ton of plasma in the FⅢ-P process was 68.73% of that in the plasma process, and the output of Pg activity per ton of plasma in the plasma process was 29.82% of that in the plasma process, which basically achieved the purpose of waste utilization of FⅢ-P. [Conclusion] The technical route of preparing Pg from FⅢ-P by full chromatography is feasible.

Objective To investigate the distribution and imaging manifestations of extrapulmonary bronchogenic cyst(BC)and to make differential diagnosis.Methods The data of 32 patients with extrapulmonary BC confirmed by pathology were collected.The lesion location,CT and MRI findings were analyzed and summarized.All patients underwent plain CT scan,and 27 of them underwent enhanced CT scan.Three patients underwent MRI plain and enhanced scan.Results Of the 32 patients,24 cases were mediastinal BC including 20 cases in the anterior mediastinum and other 4 cases in the posterior mediastinum.8 cases were ectopic BC,including 2 cases in the upper chest wall,4 cases in the gastric cardia,1 case in the greater curvature of the stomach,and 1 case in the left adre-nal gland.All lesions were single with clear boundary.The lesions were mainly round in shape(22 cases),and a few were flat/"D"shape(10 cases).There were no significant differences in the included signs between mediastinal BC and ectopic BC(P＞0.05).Nodular calcification of cyst wall was found in 2 cases.There were 4 cases with CT value＜20 HU and other 28 cases with CT value≥20 HU.The enhanced CT scan in 27 cases showed non-or mild enhancement.MRI showed hypointensity on T1WI in 2 cases,isointensity on T1WI in 1 case,hyperintensity on T2WI in 3 cases,and obvious enhancement on T1WI enhanced scan in 1 case.In addition,30 cases(93.7％)were misdiagnosed as thymic cyst(8 cases),thymoma(12 cases),neurogenic tumor(4 cases),ganglioneuroma(4 cases)and gastric stromal tumor(2 cases).Conclusion Extrapulmonary BC is rare,and most of the lesions are located near the central axis of the body with no obvious enhancement and sometimes cyst wall calcification,which has certain value for clinical diagnosis.

Curettage is the main treatment method for oral maxillofacial cystic lesions,but simple curettage may easily damage surrounding structures such as adjacent teeth and nerves,leading to incomplete removal of the cyst and large jaw defects.The curettage assisted by endoscopy can provide a good surgical field for the surgeons,can clearly identify the important anatomical structure during the operation and can remove the cyst wall tissue as much as possible,thereby reducing the damage and reducing the recurrence rate of the lesion.This article combines the characteristics of maxillofacial surgery with clinical treatment experience,summarizes relevant literature from both domestic and international sources,and engages in discussions with experts in order to provide reference for the clinical treatment of jaw cystic lesions with endo-scope assisted curettage.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objective To explore the correlation between malignant tumors and serum N-terminal pro-brain natriuretic peptide(NT-proBNP)levels.Methods A total of 336 patients with malignant tumors(cancer group)who were admitted to the Department of Cardiology,Chinese PLA General Hospital and underwent coronary angiography from January 1,2009 to December 31,2020,and were newly diagnosed and had not received any anti-tumor treatment were selected.They were matched with 1 008 patients(non-cancer group)in a 1:3 ratio using propensity score matching based on gender and age.Clinical data of the patients were collected,including age,gender,serum NT-proBNP,left ventricular ejection fraction(LVEF),SYNTAX score,serum creatinine,and tumor diagnosis information.The patients were divided into 4 groups based on the quartiles of NT-proBNP levels:low-level group(NT-proBNP ≤ 61.80 pg/mL),medium-level group(61.80 pg/mL＜NT-proBNP≤ 152.95 pg/mL),high-level group(152.95 pg/mL＜NT-proBNP≤470.10 pg/mL),and very high-level group(NT-proBNP＞470.10 pg/mL).Ordered logistic regression analysis was used to analyze the correlation between malignant tumors and serum NT-proBNP.Results A total of 1 344 patients were included,with an average age of(65.78±9.18)years old,1 003 males(74.63％),LVEF of 60.00％(55.00％,64.00％),SYNTAX score of(13.84±11.63)points,and creatinine level of 76.60(66.50,88.88)μmol/L.Among the 336 cancer patients,the top 3 types of cancer were lung cancer(84 cases,25.00％),colorectal cancer(58 cases,17.26％),and gastric cancer(52 cases,15.48％).The NT-proBNP levels in the cancer group were significantly higher than those in the non-cancer group(208.45[85.75,601.83]pg/mL vs 134.35[57.18,430.23]pg/mL,P＜0.001).Ordered logistic regression analysis showed that in the unadjusted model,malignant tumors were significantly associated with higher NT-proBNP levels(OR=1.561,95％CI 1.538-1.584,P＜0.001);after adjusting for relevant factors,malignant tumors remained significantly associated with higher serum NT-proBNP levels(OR=1.384,95％CI 1.070-1.791,P=0.013).Conclusions NT-proBNP in malignant tumor patients is higher than that in non-malignant tumor patients,and there is a significant correlation between malignant tumors and serum NT-proBNP levels.

Objective:To investigate the role of serotonin reuptake transporter(SERT)and P2X3 receptor of dorsal root ganglion(DRG)in regulating visceral hypersensitivity of rats with irritable bowel syndrome(IBS)by electroacupuncture(EA). Methods:Male Sprague-Dawley and SERT-/-rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.Three weeks post-modeling,interventions including EA,intrathecal injection,and EA plus intrathecal injection were applied,respectively.Hematoxylin-eosin staining and abdominal withdrawal reflex(AWR)score were used to confirm the successful establishment of the IBS model.AWR score,whole-cell patch clamp technique,and Western blotting assay were used to evaluate the changes in visceral pain sensitivity,electrophysiological properties of DRG neurons,and the expression of DRG P2X3 receptor and SERT in IBS rats. Results:Compared to the model group,the AWR score in the EA group decreased significantly(P<0.05),the resting membrane potential(P<0.05)and the number of action potentials(P<0.05)of DRG neurons reduced,and the baseline intensity increased(P<0.05);additionally,the expression of P2X3 receptor in DRG decreased(P<0.01),and the SERT expression increased(P<0.05).Compared to the P2X3 receptor agonist group,the SERT protein expression in DRG was higher in the EA group.In SERT-/-rats,the P2X3 receptor expression in DRG increased in the EA group compared to the model group(P<0.01). Conclusion:EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats.This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.

Objective:To explore health utility value, evaluate health-related quality-of-life(QOL)of pediatric liver transplantation(LT)recipients and examine its influencing factors to provide rationales for related health economic evaluations.Methods:This cross-sectional QOL was conducted through a questionnaire in pediatric LT recipients aged 5-17 years.The interviewees undergoing initial LT from June 2013 to September 2021 were reviewed regularly.Those children and their parents unwilling to participate or failing to understand the contents of questionnaire were excluded.The questionnaire was designed on the basis of Child Health Utility 9D Instrument(CHU9D)and answered online by one of primary caregiver.Chinese score system of CHU9D was employed for converting the responses into health utility values and the influencing factors were analyzed.Univariate analysis was performed by nonparametric tests and multivariate analysis by multiple linear regression model. P<0.05 was deemed as statistically significant. Results:A total of 140 valid questionnaires were obtained.Mean age of pediatric LT recipients was(7.95±2.74)years and mean postoperative time(4.90±2.17)years.Among them, 19 cases had experienced acute rejection and 101(72.1%)cases were living-related LT recipients.CHU9D scale indicated that average health utility value was(0.85±0.14)points.Univariate analysis revealed that age( P=0.008), education level( P<0.001)and primary disease( P=0.010)influenced the postoperative level of QOL.Multivariate analysis indicated that QOL was correlated with education level(behind schedule: 95% CI: -0.146, -0.034, P=0.002; leave of absence: 95% CI: -0.251, -0.068, P=0.001). Conclusions:Health utility of pediatric LT recipients is high with an excellent QOL.Poor QOL is associated with absence from school or dropping out of school.